Tovorafenib CAS# 1096708-71-2 6-氨基-5-氯-N-[(1R)-1-[5-[[[5-氯-4-(三氟甲基)-2-吡啶基]氨基]羰基]-2-噻唑基]乙基]-4-嘧啶甲酰胺

Tovorafenib is a potent, oral type II RAF kinase inhibitor that in biochemical assays inhibits mutant BRAF V600E, wild-type BRAF and CRAF with low-nanomolar IC₅₀ values (≈7.1, 10.1 and 0.7 nM, respectively) and suppresses MAPK signaling (pERK) and proliferation in BRAF-mutant cancer cell lines in vitro. In cellular models with certain RAS mutations it shows moderate pathway inhibition, generally without paradoxical MAPK activation seen with type I inhibitors. In vivo, tovorafenib induces strong, sustained pERK inhibition and significant antitumor effects in multiple BRAF-mutant and BRAF-fusion xenograft models, including regression of established BRAF-mutant melanoma tumors at clinically relevant oral doses; however, it shows limited efficacy in NF1-loss models without combination therapy. Tumor regrowth after dosing cessation indicates a need for continuous exposure for maintained efficacy